Until recently, plasma exchange was the gold standard treatment for patients with Guillain-Barr syndrome (GBS). The PSGBS Trial Group (Professor RAC Hughes, Coordinator; D Cornblath, Trial Design Committee and EMG Coordinator) recently finished and published a trial comparing plasma exchange, intravenous immunoglobulin, and the combination of the two therapies. While all three treatments were statistically equivalent in analyses of outcome providing definitive evidence for the use of intravenous immunoglobulin as the preferred treatment for GBS, the combined therapy was slightly better. Unfortunately, these therapies leave about 20 percent of patients with GBS dead or disabled one year after onset. This current trial is designed to test whether a second course of immunoglobulin, which mimics the combined therapy in the PSGBS trial, will hasten recovery further and reduce the long-term morbidity significantly more than a single course. The Second Immunoglobulin Dose GBS Trial (SIDGBS), a placebo-controlled, blinded trial will randomize severely affected patients two weeks after the first course of immunoglobulin to receive either (1) a second course of immunoglobulin or (2) placebo. The primary outcome measures will be reduction in (1) disability measured on a seven-point disability grade scale six weeks after randomization and (2) the proportion of patients unable to walk 10 meters without aid 46 weeks after randomization. The sample sizes needed to detect clinically meaningful changes in these outcomes at the 5 percent level of significance and with a power 80 percent are 55 in each group for outcome 1 and 213 for outcome 2. To allow a margin for beaches of protocol it is proposed to randomize 500 patients in a multicenter and international study during the course of three years. The disability grade information will be collected by individuals who do not know the treatment assignment. The primary analysis will be undertaken according to the intention to treat. Secondary outcome measures will include quality of life measures and healthcare costs. The trial will form the basis of further studies of the epidemiology, clinical and neurophysiological features, and pathogenesis of GBS. This Clinical Trial Planning Grant Application will support the development of a detailed clinical trial research plan including a complete manual of operations and procedures for the SIDGBS Trial.